CCR5 coreceptor utilization involves a highly conserved arginine residue of HIV type 1 gp120

The seven-transmembrane CCR5 was recently found to double as a coreceptor for a genetically diverse family of human and nonhuman primate lentiviruses. Paradoxically, the main region of the envelope protein believed to be involved in CCR5 utilization was mapped to hypervariable region 3, or V3, of the envelope glycoprotein gp120. In this study, we addressed the question of whether functional convergence in CCR5 utilization is mediated by certain V3 residues that are highly conserved among HIV type 1 (HIV-1), HIV type 2, and simian immunodeficiency virus. Site-directed mutagenesis carried out on three such V3 residues revealed that the Arg-298 of HIV-1 gp120 has an important role in CCR5 utilization. In contrast, no effect was observed for the other residues we tested. The inability of Arg-298 mutants to use CCR5 was not attributed to global alteration of gp120 conformation. Neither the expression, processing, and incorporation of mutant envelope proteins into virions, nor CD4 binding were significantly affected by the mutations. This interpretation is further supported by the finding that alanine substitutions of five residues immediately adjacent to the arginine residue had no effect on CCR5 utilization. Taken together, our data strongly suggests that the highly conserved Arg-298 residue identified in the V3 of HIV-1 has a significant role in CCR5 utilization, and may represent an unusually conserved target for future anti-viral designs.     

Improvement of sini decoction on hemorheology following percutaneous transluminal coronary angioplasty

OBJECTIVE: To study the hemorheological effects of Sini decoction on patients following percutaneous transluminal coronary angioplasty (PTCA). METHODS: Forty-six patients were randomly divided into Sini decoction and control groups. The hemorheologic variables were determined before and after Sini decoction treatment. RESULTS: No hemorheologic changes were observed in the patients (n = 23) only with PTCA, but the patients (n = 23) with Sini decoction were found to be significantly decreased in whole blood viscosity and red cell aggregation and dredging the blood of microcirculation as post-PTCA compared to pre-PTCA. CONCLUSION: Sini decoction could improve the patient's hemorheology.     

Prolonged survival in selected patients following surgical resection for pulmonary metastasis from hepatocellular carcinoma

BACKGROUND: Pulmonary metastasis is the commonest site of extrahepatic spread from hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the efficacy of surgical management in patients with solitary pulmonary metastases from HCC. METHODS: This was a retrospective study of patients with HCC admitted for hepatectomy from July 1972 to June 1995. The records of patients who had a pulmonary resection for histologically proven pulmonary recurrence after curative hepatectomy were selected for analysis. RESULTS: In the study interval, 380 patients with HCC underwent hepatectomy. Some 48 patients (12.6 per cent) developed pulmonary metastases documented pathologically or radiologically. Nine (seven men and two women) were suitable for curative pulmonary resection. The median disease-free survival between hepatectomy and appearance of the lung metastasis was 21 months. The median survival after pulmonary resection was 42 months, and the 1-, 2- and 5-year survival rates were 100, 78 and 67 per cent respectively. CONCLUSION: Pulmonary resection for metastases from HCC resulted in long-term survival in these highly selected patients.     

Association between bleomycin hydrolase and Alzheimer's disease in caucasians

A recent study showed modest evidence for an increased frequency of the bleomycin hydrolase (BH) V/V genotype in Alzheimer's disease (AD) patients compared with non-demented controls. To test this hypothesis, we examined this polymorphism in 621 rigorously evaluated patients and 502 control subjects (all caucasian) but were unable to detect an association between BH and AD even after controlling for age, gender, and apolipoprotein E (ApoE) genotype. We conclude that this polymorphism does not account for inherited susceptibility to AD in the populations represented in this sample.     

Clinical response of localized recurrent periodontitis treated with scaling, root planing, and tetracycline fiber

The purpose of this study was to compare the clinical efficacy of scaling and root planing alone versus tetracycline fiber therapy used adjunctively with scaling and root planing in the treatment of nonresponsive active periodontitis in patients under supportive periodontal therapy. Thirty patients who were receiving supportive treatment and had at least two nonadjacent periodontitis sites with a probing depth of between 4 and 8 mm and bleeding on probing, or had aspartate aminotransferase (AST) levels above 800 microIU in the gingival crevicular fluid in separate quadrants participated in this study. For each patient, the test sites were treated with scaling and root planing plus tetracycline fibers while the control site was treated with scaling and root planing only. Probing depths, clinical attachment levels, gingival recession, AST levels, and bleeding on probing were recorded and subgingival plaque samples were collected at baseline and 1, 3, and 6 months following treatment. At 3 months after treatment, there was a reduction of bleeding on probing and probing depth, and a gain of clinical attachment in both test and control sites. The mean reduction in probing depth of the test sites was 1.38 mm and the attachment gain was 0.8 mm after 6 months. The clinical response obtained at 3 months following therapy was maintained throughout the 6-month follow-up period. However, there were no statistically significant differences between sites treated with scaling and root planing alone and those treated with combined tetracycline therapy. Most of the reductions of probing depths in the fiber group were attributed to gingival recession. The present study did not confirm the efficacy of adjunctive tetracycline fibers in treating nonresponsive sites in maintenance subjects with regard to probing depth reduction or clinical attachment gain. Reinfection of the pockets from untreated sites and extra-crevicular regions may explain the insignificant response to local tetracycline therapy.     

Neuroimaging in children with congenital disorders of the peripheral visual system

The study investigates the neurological substrate in children with congenital disorders of the peripheral visual system (CDPVS), i.e. disorders of the anterior visual pathways and the globe. The design is retrospective; brain MRI and/or CT scans were traced and reviewed for 79 of 254 children with CDPVS on our database. The neuroradiological findings were considered in the context of degree of visual impairment (profound [PVI] and severe [SVI]), developmental outcome (setback and non-setback), and mode of imaging (MRI and CT). Scans were abnormal in 40 of 79 (51%) children; 23 of 40 (58%) had more than one lesion; and in some children lesions not previously reported were found. The number of abnormalities per child was significantly higher in the PVI than the SVI group (P<0.05); the level of significance varied according to the method of scanning (MRI, P<0.001; CT, ns). Seven children were known to have had developmental setback; significantly more brain abnormalities per child were found in the group with setbacks than in the group without (P<0.001). Eighty-six percent (24 of 28) of MRI compared with 38% (22 of 58) of CT scans were abnormal. MRI detected more lesions per child than CT (P< 0.001). Thus, a significant amount of brain pathology occurs in children with CDPVS. The number of lesions varies directly with degree of visual impairment and both correlate with developmental outcome. As brain pathology will be only one of many factors influencing developmental progress in visually impaired children, prospective multifactorial studies of the CDPVS population, which include MRI studies of the neurological substrate, will be required to clarify the latter.     

Cardio-ventilatory control in rainbow trout: II. Reflex effects of exogenous neurochemicals

The effects of various neurochemicals were examined in intact, unanesthetized rainbow trout (Oncorhynchus mykiss) to assess the role of branchial O2-sensitive chemoreceptors in the cardio-ventilatory responses to exogenous neurochemicals. cyanide stimulated ventilation and elicited bradycardia when give externally but only stimulated ventilation when injected internally. Norepinephrine increased heart rate, blood pressure and ventilatory rate but opercular pressure was not affect. Dopamine had no effect on either heart or ventilatory rate but increased blood pressure and decreased opercular pressure. Serotonin stimulated heart rate and ventilation but decreased blood pressure. Acetylcholine and nicotine stimulated all cardio-ventilatory variables. Muscarine decreased heart rate and blood pressure and had a biphasic effect on ventilation. These results, combined with the results from the preceding study, suggest that the cardio-ventilatory effects of exogenously administered (1) cyanide are entirely mediated by gill O2 receptors, (2) serotonin, and cholinergic drugs could be partly mediated by O2 receptors and (3) catecholaminergic drugs are not mediated by O2 receptors.